inthought master template...checkmate-901 recruiting, 990 pts, nivo/ipi v. nivo/chemo v. chemo nile...
TRANSCRIPT
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inThought CapabilitiesMay 2020
Oncology
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What Makes inThought Unique?
A multidisciplinary team of 16 subject matter experts with deep therapeutic area expertise that provides business intelligence support to pharmaceutical, biotech, and financial companies.
business intelligence
analysis & insight
business & science
proprietary platform
Our decision support uses a variety of data points, both primary & secondary, combined with analysis & insight. This methodology allows clients to triangulate actionable intelligence and adjust strategy.
Our proprietary inVision platform allows clients to have all critical intelligence in one place, customized for their particular key questions and topics, and accessible on demand.
We understand the business and science. inThought principals are MDs, PhDs, and MBAs with clinical, research, regulatory, and Wall Street experience.
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Continuous Monitoring Conference Coverage Ad Hoc Projects
• Email alerts with analysis
• KIT and KIQ Tracking
• Social Media Monitoring (drugs, TAs, etc.)
• Competitive Monitoring Reports (launch timelines etc., updated periodically)
• Competitive Landscape Assessments
• Analyst support
• Ongoing primary interviews with competitors, physicians, & KOLs
• Focus on presenter and attendee feedback
• KOL engagement
• Booth messaging
• Future messaging
• Social Media Monitoring (conference name, TAs, drugs, etc.)
• Address KIQs and KITs
• Trial design analyses
• Primary research
• KOL interviews and social media influencer analysis
• Revenue forecasts
• Probability of approval
• Deep Dive assessments of companies, drugs, & MOAs
• Target Product Profiles
• Licensing opportunities
• Strategy workshops
• BD due diligence
inThought Competitive Intelligence ExpertiseinThought is able to support a diverse body of client work.
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inVision: Our Insights Engine
inThought has developed a customizable web-based platform, inVision, to offer clients a streamlined interface for their business intelligence. The platform allows our subject matter experts to rigorously collect, organize, track, and integrate information from multiple sources, viewed longitudinally. With inVision, you can quickly find everything you need to help you answer important tactical and strategic questions.
How does it work?
First, we identify project requirements and set parameters and key intelligence questions (KIQs) in inVision based on your interests.
As new information is obtained, it is parsed and tagged to your KIQs and other topics of interest. This process is managed by inThought’s therapeutic area experts.
Analysis is added to each piece of information, creating a searchable history of the material relevant to a given topic.
New findings added to the tool generate email alerts to your team, offering you convenient, forward-looking reports on the news—but more importantly, our expert analysis on how it may alter the landscape and impact your programs.
In addition to email alerts and project deliverables, you can always view your information and analysis in a consolidated, searchable format within the platform.
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Continuous Monitoring Email Alerts
inVision connects CI teams to timely alerts and strategic implications based on therapeutic areas, clinical trials, and MOAs of interest.
• inThought analysts continually monitor corporate press releases, investor presentations, conference abstracts, and clinical trial records to provide timely analysis of relevant events
• Analysis is customized and includes implications that are specific to the client’s portfolio
• These alerts are prioritized on inVision as High, Medium, and Low priorities and emailed to client’s CI teams
• inVision allows CI teams to keep a pulse on key therapeutic areas, clinical trials, and MOAs
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News Alert Example
▪ Xxx
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inVision Dashboard Example
Curated documents for the site
Provides a place to recall alerts and
posts
Links to conference data
Topic folders to organize by theme
Link to Up-to-date KIQs
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Conference Coverage Capabilities
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Conference CoverageCustomized inVision Homepage
• Conference coverage schedules are customized based on client keywords and KIQs
• Schedules are uploaded to the inVision platform to allow the inThought analyst to capture presentation/poster images and notes
• Attending internal client members can also access inVision to input their own notes and images
• Presentations/posters are organized by key themes on inVision
The inVision conference homepage is customized based on the client’s key intelligence themes (KITs) and key intelligence questions (KIQs).
Key Themes
inVision Conference LayoutOverviewKOL contact notes
for primary insights
Topic folders to organize presentations by theme
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Conference CoverageSession / Poster Overview
Session Title / Speaker / Time / LocationAnalyst Analysis
Presentation / Poster Images
Overview
• Posts are color coded based on importance and tagged to key themes
• The analyst’s notes and images are compiled in one central location within the relevant session
• Theses notes/images can be searched on inVision by keyword, priority, and type
• Team members can view the entire post, review images, and download or email images to colleagues
Conference coverage is centralized on inVision, allowing both inThought analysts and internal client team members to simultaneously contribute images, notes, and view schedules.
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Conference Coverage on Mobile DeviceThe inVision conference coverage on a mobile device is similar to the web-based layout. Notes can be directly drafted in inVisionor cut and pasted from other apps, such as Notes. Images can be taken in inVision or added through photos on the mobile device.
Icon on mobile homepage Mobile layout Notes function Adding images
inVision icon
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Virtual Conference Coverage
• inVision provides links to virtual presentations, whether the conference is virtual or if team members are attending “virtually.”
• The debrief function allows the selection of key information, including pictures of data, to be combined with summary text and analysis in a virtual debrief. Insights from the debrief can be incorporated into the conference project.
• A virtual conference tour can be constructed with key summaries and pictures to provide a quick summary of conference highlights with the ability to delve into more detailed information
The inVision conference site has features enabling coverage of virtual conferences. These features also allow for attending conferences “virtually” as well as conducting virtual conference debriefs
Overview Virtual Debrief/Conference Summary Virtual Presentations
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ASCO 2019 Highlights
▪ TIM-3 and CD73 had low profiles– The design of an ongoing Lilly trial investigating its TIM-3/PD-1
bispecific were presented.
– Hypothesis-generating work from academic groups point to CD73 as a potential target in RCC and urothelial carcinoma.
▪ Efforts to develop new checkpoint inhibitors may be shifting to focus on PD-1 axis inhibitor experienced patients
– This makes strategic sense as the number of such patients grows and especially for companies aiming to establish a foothold in the competitive IO space. Examples of these approaches featured at ASCO included:
▪ Immutep LAG-3/PD-1 combo in PD-1 axis inhibitor experienced NSCLC
▪ Novartis LAG-3/PD-1 combo in tumor types with a “suboptimal response to checkpoint blockade monotherapy”
▪ F-star LAG-3/PD-L1 bispecific in PD-1 axis failures
▪ Lilly TIM-3/PD-L1 bispecific, enrollment in dose expansion requires prior treatment with PD-1 axis inhibitor if such treatment is on label
Checkpoint Inhibitors
▪ LAG-3 clinical data are beginning to emerge as other programs showcased the designs for ongoing trials
– Early readouts from Regeneron and Novartis showed hints of activity for in-house anti-LAG-3/PD-1 combos. It is not yet clear, however, what the exact contribution of LAG-3 inhibition is, however.
– Immutep (LAG-3 fusion protein) and F-star (LAG-3/PD-L1 bispecific) trials are ongoing.
– LAG-3 expression requirements were not evident in any of the presentations.
▪ A2AR programs are also beginning to generate clinical data
– Corvus and Arcus presented initial results indicating early evidence of activity.
– A Corvus study is requiring A2AR expression in the dose-expansion phase.
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ASCO 2019 Session Example
AB928, a novel dual adenosine receptor antagonist, combined with chemotherapy or AB122 (anti-PD-1) in patients (pts) with advanced tumors: Preliminary results from ongoing phase I studies (#2604)
Early evidence of activity demonstrated by Arcus’ dual adenosine receptor antagonist
▪ This Arcus poster summarized initial clinical data from three ongoing phase 1 studies investigating the company’s A2AR/A2BR small molecule antagonist, AB928, used in combination with chemotherapy or an anti-PD-1 mAb, AB122.
▪ 26 patients have been treated in dose-escalation phases of the studies. The MTD has not yet been identified. One DLT (Grade 2 rash in the PD-1 combo study) has been documented.
▪ In the PD-1 combo study, one PR occurred in nine evaluable subjects. The responding patient has mixed Mullerian endometrial cancer.
inThought Assessment: The impact of inhibiting A2BR, in addition to A2AR, remains unknown. The single PR in the PD-1 combination of the study is encouraging, but more data are required to fully assess the potential of this strategy.
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Conference CoverageKey Intelligence Questions (KIQs)inVision maintains a repository of client’s KIQs and relevant answers.
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Bladder Cancer
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Example: Bladder Cancer Marketed Products
Agent Company MOA/ROA ApprovedApprovedCountries
WW Sales ($, billions)*Patent Exp.
2018A 2019E 2020E
Keytruda(pembrolizumab)
Merckanti-PD-1 mAb
IV
• 1st line (cisplatin ineligible)
• 2nd lineU.S., EU, Japan 7.2 10.8 14.4
2028 U.S.2030 EU
Opdivo(nivolumab)
BMSanti-PD-1 mAb
IV• 2nd line U.S., EU 6.7 7.3 7.2
2028 U.S.2028 EU
Tecentriq(atezolizumab)
Rocheanti-PD-L1 mAb
IV
• 1st line (cisplatin ineligible)
• 2nd lineU.S., EU 0.8 1.7 2.5 2028
Imfinzi(durvalumab)
AstraZenecaanti-PD-L1 mAb
IV• 2nd line
U.S., Canada(Accelerated
Approval)0.6 1.4 2.0
2030 U.S. 2030 EU
Bavencio(avelumab)
Pfizer / Merck KGaA
anti-PD-L1 mAbIV
• 2nd line U.S. 0.0 0.06 0.152033 U.S. 2032 EU
Balversa(erdafitinib)
JanssenFGFR1-4 kinase inhibitor
PO• 2nd line (FGFR mut) U.S. n/a 0.05 0.09 unknown
Sources: Adis, Bloomberg, NCCN Guidelines, company reports, Drug Prescribing Information*Keytruda, Opdivo, Tecentriq, Imfinzi, and Bavencio are each approved for many tumor types; bladder cancer contribution to total revenue is not known; 2019 and 2020 figures are Bloomberg consensus estimates
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Development Program Overview: Bladder CancerLine-of-Therapy Analysis
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Keytruda (pembrolizumab)
Merck
Tecentriq(atezolizumab)
Roche
Opdivo(nivolumab)
Bristol-Myers
Imfinzi(durvalumab)AstraZeneca
Bavencio(avelumab)
Pfizer/Merck KGaA
LoT Anti-PD-1 mAb; IV Anti-PD-L1 mAb; IV Anti-PD-1 mAb; IV Anti-PD-L1 mAb; IV Anti-PD-L1 mAb; IV
1st Line
KEYNOTE-052 active, 374 pts, single-arm
IMvigor210 (Cohort 1) active, 119 pts
CHECKMATE-901 recruiting, 990 pts, nivo/ipi v.
nivo/chemo v. chemo
NILE recruiting, 885 pts, durva/gem/carbo or cisplat v. durva/gem/carbo/tremelimumab v. gem/carbo or cisplat
(SoC)
JAVELIN Medley VEGF active, 59 pts, single-arm,
Bavencio/InlytaKEYNOTE-361 active, 990 pts, pembro v. pembro/chemo v.
chemo IMvigor130 active, 1,200 pts,
atezo v. [atezo/gem. + carbo or cisp.] v. [gem.+ carbo. or
cisp.]
DANUBE recruiting, 1,200 pts, durva v. durva/treme v.
chemo
JAVELIN Medley Chemotherapy recruiting, 80
pts, single-arm, avelumab/gem/cisplatin
LEAP-011 recruiting, 694 pts, pembro/lenvatinib v. pembro BAYOU active, 152 pts,
durva/olaparib v. durva
2nd LineKEYNOTE-045 active, 542 pts,
pembro v. [pacli. or vin. or doce.]
IMvigor210 (Cohort 2) active, 310 pts
CHECKMATE-275 active,
386 pts
Study 1108 active, 182 pts in cohort
JAVELIN Solid Tumor active, 161 pts in cohortMORPHEUS UC recruiting,
305 pts, enfortumab/atezo v. multiple
3rd line
P3Market FailedP2 P1/2
Keytruda and Tecentriq dominate IO use in the first-line setting, however Imfinzi’s three late-stage combination regimens may soon enter this space.
Sources: clinicaltrials.gov
https://clinicaltrials.gov/ct2/show/NCT02335424https://clinicaltrials.gov/ct2/show/NCT02951767https://clinicaltrials.gov/ct2/show/NCT03036098https://www.clinicaltrials.gov/ct2/show/NCT03682068https://clinicaltrials.gov/ct2/show/NCT03472560https://clinicaltrials.gov/ct2/show/NCT02853305https://clinicaltrials.gov/ct2/show/NCT02807636https://clinicaltrials.gov/ct2/show/NCT02516241https://clinicaltrials.gov/ct2/show/NCT03317496https://www.clinicaltrials.gov/ct2/show/NCT03898180https://clinicaltrials.gov/ct2/show/NCT03459846https://clinicaltrials.gov/ct2/show/NCT02256436https://clinicaltrials.gov/ct2/show/NCT02108652https://clinicaltrials.gov/ct2/show/NCT02387996https://clinicaltrials.gov/ct2/show/NCT01693562https://clinicaltrials.gov/ct2/show/NCT01772004https://clinicaltrials.gov/ct2/show/NCT03869190
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Bladder Cancer Pipeline Timeline
Sources: Adis, Bloomberg, company reports, inThought internal estimates
Agent / Company Study / Line TreatmentStart -
Primary Comp.
2020 2021 2022 2023 2024 2025+
1H 2H 1H 2H 1H 2H 1H 2H 1H 2H 1H 2H
Imfinzi (durvalumab)AstraZeneca
DANUBE1st line
Imfinzi v. Imfinzi/treme
v. chemo
Nov 2015-Sept 2019
NILE1st line
Imfinzi/chemo v. Imfinzi/treme-
limumab/chemo v. chemo
Sept 2018-Apr 2022
Bempegaldesleukin(NKTR-214)Nektar / BMS
PIVOT-101st line
NKTR-214/ Opdivo
Apr 2019-Nov 2020
Enfortumab vedotinSeattle Genetics / Astellas
EV-2012nd and 3rd line
single agentOct 2017-Nov 2020
EV-3013rd line
single agentJune 2018-Sept 2021
Opdivo(nivolumab)Bristol-Myers
CheckMate-9011st line
Opdivo/Yervoy v. Opdivo/chemo v.
chemo
Mar 2017-July 2021
RogaratinibBayer
FORT-12nd line
single agent v. chemo
May 2018-Nov 2020
= Top line Data = Projected Filing
= Projected Launch (U.S., EU)
Nektar intends to seek Accelerated
Approval in U.S. based on Phase 2 data
Received Accelerated Approval on Dec 19, 2019 (3L)
https://clinicaltrials.gov/ct2/show/NCT02516241https://www.clinicaltrials.gov/ct2/show/NCT03682068https://clinicaltrials.gov/ct2/show/NCT03785925https://clinicaltrials.gov/ct2/show/NCT03219333https://clinicaltrials.gov/ct2/show/NCT03036098https://clinicaltrials.gov/ct2/show/NCT03410693
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Agent Line N ORR (%) CR Rate (%) mPFS (mon) mOS (mon) mDoR
Tecentriq/platinum-chemo1
(IMvigor130; ESMO 2019)1st line 451 47.4% 12.5% 8.2 16 (NS) ---
Enfortumab vedotin/Keytruda2
(EV-103; ESMO 2019)1st line 45 71% 13% --- --- ---
Bempegaldesleukin/Opdivo3
(PIVOT-02; ASCO-GU 2019)1st line 27 48% 19% --- --- ---
Enfortumab vedotin4
(EV-201; ASCO 2019)
PD-1/L1
experienced125 44% 12% 5.8 11.7 7.6
Sacituzumab govitecan5
(TROPHY-U-01; ESMO 2019)2nd line+ 41 34% --- 7.2 15.5 12.9
Tislelizumab6
(Phase 2; ESMO 2019)2nd line+ 104 23.1% 7.7% 2.1 9.8 NR
RC48-ADC7
(Phase 2; ASCO 2019)
2nd line+
HER2+43 60.5% --- NR --- ---
Vofatamab/Keytruda8
(FIERCE-22; ASCO 2019)2nd line+ 22 36% 0% --- --- ---
Rogaratinib9
(Phase 1; ASCO 2018)All 51 24% --- --- --- ---
Notes: NS = not statistically significant; NR = Not Reached
Efficacy Comparison: Pipeline AgentsBladder Cancer
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Endometrial Cancer
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Endometrial Cancer Marketed Products
Sources: UpToDate, NCCN Guidelines*Keytruda and Lenvima are each approved for multiple tumor types; endometrial cancer contribution to total revenue is not known; 2019 and 2020 figures are Bloomberg consensus estimates; Lenvima figures relate to Eisai’s FY18, FY19, and FY20 (ending March 31 of 2019, 2020, 2021, respectively)^Supplementary protection certificates valid until 2026 have been filed and issued in some EU countries
Agent Company MOA/ROA ApprovedApprovedCountries
WW Sales ($, millions)*Patent Exp.
2018 2019 2020
Keytruda(pembrolizumab)
Merckanti-PD-1 mAb
IV
• 2nd line+ advanced non-dMMR or MSI-H endometrial cancer (with lenvatinib)
U.S., Australia, Canada
7,171 10,778 14,3772028 U.S.2030 EU
Lenvima(lenvatinib)
Eisai/ Merck
PDGFR, FGFR1-4 antagonist
oral
• 2nd line+ \ advanced non-dMMR or MSI-H endometrial cancer (with pembrolizumab)
U.S., Australia, Canada
580 1,034 1,4932025 U.S.2021 EU^
2026 Japan
1L: Current treatment regimens for advanced non-resectable endometrial cancer are defined by histological risk-assessment:
– Low-risk: Most tumors are resectable, with favorable prognosis. Following resection, some patients chose progestin therapy to preserve fertility.
– Intermediate-risk: post-operative pelvic radiation therapy (PRT). High-intermediate risk are sometimes offered cyclophosphamide, doxorubicin, and cisplatin therapy (CAP).
– High-risk: Multiple cycles PVT or vaginal brachytherapy (VBT). Most clinicians follow with 3-6 cycles paclitaxel + carboplatin.
Recurrent: Keytruda/Lenvima are approved in the U.S. for 2L+ advanced non-dMMR/MSI-H tumors. SOC is paclitaxel + carboplatin.
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Endometrial Cancer Pipeline Timeline
Sources: Adis, Bloomberg, company reports, inThought internal estimates
Agent / Company Study / Line TreatmentStart -
Primary Comp.
2020 2021 2022 2023 2024 2025+
1H 2H 1H 2H 1H 2H 1H 2H 1H 2H 1H 2H
dostarlimabGSK (Tesaro)
RUBY1st line
+ paclitaxel plus
carboplatinJul 2019
GARNET2nd line+
Single agent Mar 2016
Keytruda (pembrolizumab)
Merck
ENGOT-En91st line
+ lenvatinib vs. paclitaxel plus
carboplatinApr 2019
KEYNOTE-7752nd line
+lenvatinib vs. paclitaxel or doxorubicin
Feb 2022
Lenvima (lenvatinib)Eisai
ENGOT-En91st line
+ pembro vs. paclitaxel plus
carboplatinApr 2019
KEYNOTE-7751st line
+pembro vs. paclitaxel or doxorubicin
Feb 2022
Xpovio (selinexor)Karyopharm
SIENDO1L/2L maint.
single agent Jan 2018
= Top line Data = Projected Filing
= Projected Launch (U.S., EU)
GSK (Tesaro) intends to file for approval based on positive Phase 2 arm data; U.S
approval could come in mid-2020.
https://clinicaltrials.gov/ct2/show/NCT03981796https://clinicaltrials.gov/ct2/show/NCT02715284https://clinicaltrials.gov/ct2/show/NCT03884101?term=keytruda&cond=endometrial+cancer&draw=2&rank=12https://clinicaltrials.gov/ct2/show/NCT03517449https://clinicaltrials.gov/ct2/show/NCT03884101?term=keytruda&cond=endometrial+cancer&draw=2&rank=12https://clinicaltrials.gov/ct2/show/NCT03517449https://clinicaltrials.gov/ct2/show/NCT03555422
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Additional Sample Work
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Competitive Landscape: Deep Dive Overviews
Pipeline Views (Preclinical and Clinical)
Program Analysis by Line of Therapy
Current Treatment Recommendations
Efficacy and Safety Comparisons
Clinical Trial Overviews
Executive Summaries
Primary Research
Strategy Workshops
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Executive Summaries
inThought’s executive summaries highlight the key findings of indication or MOA specific competitive monitoring reports, as well as implications to the client’s portfolio.
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▪ Anti-fibrotic
Ph 1
Ph 2
Ph 3Oclavia (Intercept)
Elafibranor (Genfit)
Cenicriviroc (Allergan)
Aramchol(Galmed)
MGL-3196 (Madrigal)
JBK-122 (TaiwanJ)
Oltipraz (PharmaKing)
Cenicriviroc+tropifexo
(AGN / NVS)
Tropifexo (Novartis)
EDP-305 (Entana)
Seladelpar (CymaBay)
EDP-305 (Entana)
Cilofexor (GS-9674)
DS102 (Afimmune)
Lanifibran
or
(Inventiva)LMB-763
(Novartis)
Pegbelfermin (BMS)
ORMD-0801 (Oramed)
AKR-001 (Akero)
BIO89-100 (89bio)
MK-3655 (MGM & Merck)PXL-065 (Paxel)
Remoglifloxin (Avolynt)
MT-3995 (Mitsubishi Tanabe) NS0200 (NuSirt)
MSDC-
0602K
(Cirius)NGM-282
(NGM)
LIK-066 (Novartis)
Semaglutide (Novo Nordisk)CORT118335 (Corcept)
Saroglitazar (Zydus)
GS-0976 (Gilead)
Volixbat (Mirum)
VK2809 (Viking)
PF-05221304 (Pfizer)
Icosabutate (NorthSea)
IONIS-DGAT2Rx (Ionis)
Norursodeoxycholi
c (Dr.Faulk)
PF-06835919
(Pfizer)
TVB-2640 (3-
V) ANGPTL3-LRx
(Ionis)
Gemcabene
(Gemphire)HTD-1801 (HighTide)
Pemafibrate
(Kowa)SNP-610
(Sinew)GRI-0621 (Gri Bio)
JKB-121 (TaiwanJ)
Pentamidine
(Vertyx)
SGM-109 (Second
Genome)
Namodenosen
(Can-Fite)
Tipelukast
(MediciNova)
CER209 (Cerenis)
EYP001 (Enyo)
TERN 101 (Terns)
PF-07055341
(Pfizer)
PF-06865571 (Pfizer)
MK3655 (Merck)
HM 15211 (Hanmi)
Nimacimab (CB1r
antagonist,
BirdRock)
BI-1467335 (Boehringer)
BI-1467335 (Boehringer)
IMM-124E (Immuron)
HepaStem (Promethra)
PXL770 (Poxel) LPCN 1144 (Lipocine)
LPCN 1148 (Lipocine)
MT-3995 (Mitsubishi Tanabe)
Foralumab (Tiziana
Life)
DUR-928 (Durect)
Belapectin(Galectin)
Pipeline Overview: NASH/NAFLD (1)
Anti-hyperglycemics Anti-hyperlipidemics Anti-inflammatory OtherAnti-fibrotics
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Mitapivat; Agios
PKR activator
ARQ 092; POArQule, Univ or Illinois
Pan-AKT inhibitor
EdX-17; parenteralEpimedX
Plant growth factor
DRX-194 DeuteRx
Deuterium stabilized single enantiomer
Undisclosed; IVMaxcyte/NIAID
Non-viral CRISPR mediated gene therapy
AIC-6020PHD Biosciences
Antioxidant (unspecified)
HBI 002; POHillhurst Bio
Heme oxygenase modulator
MEDI 6012 (ACP501); IVAstraZeneca
Recombinant human LCAT
Anti-inflammatory enzyme inhibitors; POPHD Biosciences
No designationHomology/Novartis
AAV based gene therapy
PNQ 103; POImpetis
Adenosine A2B receptor antagonist
NM-96; POPHD Biosciences
Antioxidant
VacnoSynZyme Technologies
Caged NO labeled albumin
No designation; POOrphagen Pharmaceuticals
Orphan nuclear receptor antagonists
No designationFulcrum Therapeutics
Small molecule gamma globin activator
No designationPharmaEssentia
Unknown MOA & ROA
RCY-1497; PORegenacy
HDAC1/2 inhibitor
CAL-H (CSL200); IVCSL
Lentiviral Gene Therapy
No designation; IVCSL Behring
Plasma derived haptoglobin and hemopexin
No designation; IVGenethon/INSERM, Stanford U
Lentiviral gene therapy targeting HBB
Trichosic; POErrant Gene Therapeutics
HDAC inhibitor (unspecified)
EMZ8266; POEpizyme
EHMT2 (G9a) inhibitor
No designationIntellia/Novartis
CRISPR/Cas9 targeting BCL11A
Keap1ASOIonis
Antioxidant genes inducer
No designation; IVEditas
CRISPR/CAS9 targeting HBB
HBI-137; IVHillhurst Bio
CO therapy, Heme oxygenase 1 modulator
ORY3001 (OG-S1355); POOryzon
LSD1 inhibitor
VBP15A, VamaroloneReveraGen
Glucocorticoid receptor agonist
Klf1ASOIonis
gamma-globin inducer through regulation of BCL11A
Sirolimus (rapamycin)Rare Partners, Univ. of Ferrara
HbF inducer
MGTA-456;Magenta
Hematopoietic stem cell therapy
Luspatercept; SCAcceleron, Celgene
Modified type II activin receptor fusion protein
No designationBioverativ/Bicycle Therap.
Undisclosed
UndisclosedSyros
Single gene modulator
ProteinSmall Molecule
Monoclonal Ab
Polysaccharide
Gene TherapyRNAi / nucleic
acid
Antioxidant competitorCell Therapy
Undisclosed
Pipeline Overview: Sickle Cell DiseasePreclinical Assets
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Phase of Development(48 trials)
1 1/2 2 2/3All Early
Trials
ADC 3 2 0 0 5
Chemotherapy 2 1 1 1 5
Epigenetics 2 1 0 0 3
Hormone 0 1 0 0 1
ERi 0 0 0 0 0
SERD 0 0 0 0 0
IO 1 3 2 0 6
Novel IO 5 2 3 0 10
CDK4/6 0 0 2 0 2
Kinase (other) 4 1 4 1 10
PI3K/mTOR 0 1 0 0 1
Onc. Virus 1 0 0 0 1
PARPi 1 1 2 0 4
Targeted 0 0 0 0 0
Other 0 0 0 0 0
Unknown 0 0 0 0 0
Totals 19 13 14 2 48
• IO approaches dominant the early stage pipeline for TNBC
• Novartis leads the way in novel IO approaches. LAG525 (LAG-3) and MCS110 (M-CSF) are in a total of 3 combination trials
o Additional Novel IO targets include IL-17, CXCR2, IL-1b, PVIRG, and A2aR
• SGN-LIV1A from Seattle Genetics represents one of the most advanced ADCs in development (Phase 1/2); targeting LIV-1 expressing tumor cells and is conjugated to the anti-tubulin agent MMAE
Summary for TNBC
Novel IO = non-PD-1/PD-L1 or CTLA-4 mechanism
Pipeline Overview: MOA Deep DiveTNBC MOA Heat Map
IO approaches account for the majority of trials in TNBC, representing 33% of the pipeline.
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Target Highest Phase Company Product(s) Indication Comments
AFP 1/2 Eureka ET140202 HCC
• ARTEMIS technology is designed to regulate activity of CAR –T cells in vivo
• follow-on construct to discontinued ET1402L1
• china phase 1 showed 1 CR in 6 patients
• phase 1/2 U.S. trial opened May 2019
AXL 1/2 F1 Oncology CCT301-38 RCC
• trial opened in China Mar 2018
• being tested in same trial as CCT301-59
• uses BioAtla’s CAB technology
• trial being sponsored by Shanghai Sinobioway Sunterra
• preliminary data presented at CIMT 2019
BCMA 3bluebird/ Celgene
(BMS)idecabtagene
vicleucel (bb2121)multiple myeloma
• autologous• granted BTD and PRIME designation Nov
2017
• pivotal phase 2 KarMMa trial fully enrolled
• randomized phase 3 trial in 3L+ MM opened Oct 2018 (vs. triplet regimens; KarMMa-3)
• KarMMa-2 trial in r/r MM and high-risk MM opened Nov 2018
• U.S. filing anticipated in 1H20
• 1L MM trial planned for 2H19• BMS to acquire Celgene (transaction to close
4Q19)
Clinical Pipeline: MOA Deep DiveCAR-T Status Updates
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Keytruda Opdivo Libtayo Tecentriq Bavencio Imfinzi
mPFS mOS ORR mPFS mOS ORR mPFS mOS ORR mPFS mOS ORR mPFS mOS ORR mPFS mOS ORR
NSCLC
119,843 deaths191,646 cases
a. 1L metastatic non-sq. (+pemetrexed and PT-chemo for KEY)(+beva., paclitaxel, & carboplatin for TEC)
8.8NR; HR=0.49
48% 6.7-8.5 19.243%-55%
b. 1L metastatic sq. w/ paclitaxel
6.4 15.9 58%
c. 1L metastatic monotherapy
5.4-7.116.7-20.0
27%-39%
d. unresectable, Stage III (no progression following Pt-based and RT)
16.8NR (vs. 28.7)
e. Previously treated (2L for Opdivo)
4.0-5.212.7-17.3
19%-29%
3.5 9.2 20% 2.8 13.8 14%
f. 2L metastatic non-sq. 2.3 12.2 19%
Urothelial
18,740 deaths84,400 cases
a. 1L, cisplatin ineligible --- ---21%-47%
22%-28%
b. Previously treated (2L+)
2.1 10.3 21% 2 8.7 20%9.5%-26%
16.1% 26%
HNSCC
10,860 deaths53,000 cases
a. 1L metastatic or unresectable, recurrent +/- platinum/FU
3.2-4.912.3-
1319%-36%
b. Previously treated recurrent or metastatic
2.1 8 16% NS 7.513%NS
Efficacy Comparison: PD-1 Axis OverviewApproved Indications and Efficacy Data
Sources: Drug prescribing information, American Cancer Society statistics
Notes: mPFS and mOS in months
High unmet need
Moderate unmet need
Low unmet need
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Clinical Trial Endpoint ComparisonSickle Cell Disease
Key Endpoints
Ch
ange
in H
b
Day
s w
ith
SC
D
sym
pto
m
exac
erb
atio
n
Rat
e o
f V
OC
s re
qu
irin
g cl
inic
vis
it
Rat
e/n
um
ber
of
VO
Cs
Drug Trial Age SizeEstimated
Length
Ph
ase
3
voxelotorHOPE
NCT0303681312-65 400
2 years, 6 months 1 2
crizanlizumabSTAND
NCT0381474612+ 240
3 years,1 month 1 2
BrilintaHESTIA3
NCT036159242-17 200
2 years,1 month 2 1
SC411ASCENT
NCT026043685-17 210
1 years, 9 month 2 1
Ph
ase
1
/2 LentiGlobinHGB-206
NCT0214055412-50 50
6 years,5 months 1 2
Other Endpoints of Interest
• Opioid and non-opioid use
• Time to first crisis
• Number of ACSs (Acute Chest Syndrome)
• Overall rates of hospitalization
• Number of days hospitalized
The majority of Phase 3 SCD endpoints focus on VOCs; only voxelotor is using change in hemoglobin levels as a primary endpoint in Phase 3. LentiGlobin is also assessing Hb levels in a Phase 1/2 trial, with plans to do the same in Phase 3.
https://clinicaltrials.gov/ct2/show/NCT03036813https://clinicaltrials.gov/ct2/show/NCT03814746https://clinicaltrials.gov/ct2/show/NCT03615924https://clinicaltrials.gov/ct2/show/NCT02604368https://clinicaltrials.gov/ct2/show/NCT02140554
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Primary Research: HemophiliaUS/EU Physician Interviews (Perception of Emicizumab)
Potential in inhibitor patients, SQ administration, and the recent reported SAEs were top of mind with physicians (n=15) whenasked about their perception of emicizumab.
• “Will be a fabulous drug for patients with inhibitors. Safety is a major issue, with current information will not use it in patients without inhibitors” – German physician
• “Efficacy reports are good. Sub Q. Patients who have been in trial like the drug. Recent AE report have shaken some of the enthusiasm about the drug” – U.K. Physician
• “Home run for inhibitor patients. For non-inhibitor patients, already have a safe and effective therapy. ACE 910 needs to as safe and effective. Sub Q very important advantage” – U.S. Physician
• “Will be a big splash when it comes out, but still lot of details to be ironed out that could make a difference on how much it'sutilized.” – U.S. physician
In response to an initial question about their overall perception of emicizumab:
• 9 of 15 physicians viewed the drug as a potential game changer or potentially very beneficial for patients with inhibitors
• Only 4 physicians initially discussed emicizumab’s potential for all hemophilia A patients
• Many physicians also highlighted SQ administration as well as the potential for extended dosing
• Relative to extended dosing, most physicians and nurses discussed emicizumab as a once weekly drug
• 5 physicians mentioned the reported thrombotic SAEs up front, for some this was the first topic mentioned
0
2
4
6
8
10
Pote
nti
al
gam
echanger/ver…
SQ
adm
inis
trati
on
Recent
report
ed S
AEs
Pote
nti
al fo
rall H
em
Apati
ents
Long h
alf
life
/exte
nded
dosi
ng
Overall Perception
Q U O T E S
D E T A I L E D F I N D I N G S
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Strategy Workshops
inThought can lead competitive workshops. The exact focus and scope of these workshops will be determined by the client but could include focusing on competitive position in a specific TA, preparation for a new launch, or for a competitor launch.
inThought will work with the client to develop the design of the workshop so that it is appropriate for the attendees and effective at developing insights for the potential market
Workshop Design
inThought will prepare pre-read material for the workshop participants that will include clinical data, trial design, competitor strategy assessments, and other relevant data
Pre-read Materials
inThought will develop, in consultation with the client, the workshop deck as well as any graphics or materials necessary for the performance of the wargame
Workshop Deck and
Material
inThought team members will conduct onsite preparations either the day of or day prior to the workshopPre-workshop Prep
inThought will provide a report of the key findings and summaries from the workshop discussions one week after the workshop completionWorkshop Execution
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inThought Contact Information
Dr. Presby joined inThought in 2019. Previously, he worked for a boutique biopharma consulting firm and also completed an internship in equity research at Leerink Partners. In these roles, he has developed experience in business development assessments, forecasting, and market access.
Dr. Presby received his Ph.D. in Immunology from the Johns Hopkins School of Medicine where his thesis work focused on the discovery of biomarkers in autoimmune disease and T Cell functionality. Additionally, while at Hopkins he was a co-founder of the Johns Hopkins Biotech Investment Group (JHBIG) which focuses on preparing students for careers in equity research and venture capital. He earned his B.S. in Biology from Gettysburg College.
Matt Presby, [email protected]
1.732.690.4119
After completing his training in immunology and biochemistry, Dr. Weintraub began work as a financial analyst in 2000. Collaborating with Dr. Henderson, Dr. Weintraub co-founded BiotechTracker, an online tool for investors. In 2004, he became a licensed security analyst with Hibernia Southcoast Capital covering the biotechnology sector, and later performed the same role at Variant Research. In 2006, Dr. Weintraub joined Dr. Henderson and Dr. Zuckerman at Reuters Insight, providing analysis of drug development and trends in medicine to professional investors. Dr. Weintraub’s team moved to inThought in January 2009. Through a divestiture by Wolters Kluwer, inThought and Source Healthcare Analytics became part of Symphony Health Solutions, a healthcare information company. inThought Research LLC formed a stand-alone company in May 2014.
Prior to 2000, Dr. Weintraub was senior scientific editor for the biology research journals Cell and Molecular Cell. Dr. Weintraub performed biochemistry and immunology research at Stanford University and at the John Curtin School of Medical Research in Canberra, Australia. He earned his doctorate in Biology from the University of California, San Diego, and a Bachelor of Science in Life Science from the Massachusetts Institute of Technology.
Ben Weintraub, [email protected]
1.646.331.9234
www.inthought.com
mailto:[email protected]:[email protected]://www.inthought.com/
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inThought Contact Information
Dr. Khandan joined inThought Research in 2019. He has held previous positions as a Fellow at a life science consulting firm and as a Scientist at Editas Medicine. In these roles, Dr. Khandan built expertise in asset scouting, evaluating rare diseases and therapeutic areas, and building market access and commercial viability assessments.
Dr. Khandan received his Ph.D. in Molecular, Cellular, and Developmental Biology from the University of Colorado, Boulder. His doctoral research focused on signaling and growth factors governing retinal vascularization. He has extensive experience in CRISPR/Cas9 gene editing, stem cell differentiation, and cell therapies. Dr. Khandan received his A.B. in Chemistry from Dartmouth College.
Lavan Khandan, [email protected]
1.860.965.8007
Prior to joining inThought, Dr. Weyerbacher was a scientific consultant to biotechnology companies, providing scientific and regulatory analysis of compounds and distinct therapeutic combinations. She has previously worked as a Senior Scientist at L’Oreal Research and Development. In this role, she managed the clinical testing program of multiple consumer products and supported cross-functional teams with scientific leadership and expertise to facilitate blockbuster product launches.
Dr. Weyerbacher graduated from Skidmore College with a Bachelor’s degree in Biology-Chemistry before receiving a PhD in Pharmacology from Weill Cornell Medical College. Her dissertation research focused on the identification of critical pain signaling proteins, cytokines and immune/central nervous system interactions as relevant pharmacological targets for clinical pain control. In between college and graduate school, Dr. Weyerbacher was a Clinical Research Study Assistant at Memorial Sloan Kettering Cancer Center. In this role, she managed an active clinical trial program, defining and monitoring project scope, timelines and deliverables from project initiation to close-out. She has presented her research in pharmacology, neuroscience and oncology at several scientific conferences. Dr. Weyerbacher is the immediate past President and active member of the MetroNY Chapter of the Association for Women in Science (AWIS).
Amanda Weyerbacher, [email protected]
1.917.612.2939
www.inthought.com
mailto:[email protected]:[email protected]://www.inthought.com/
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inThought Contact Information
www.inthought.com
Mr. Schaeffer is a founding partner of inThought Research. He is responsible for identifying and developing new business opportunities, as well as expanding the presence of the company and its brand. Mr. Schaeffer has over 20 years of experience in healthcare industry consulting.
Prior to inThought, he served as Director of Institutional Sales at Symphony Health Solutions where he oversaw key pharmaceutical accounts and launched the Wall Street practice. Mr. Schaeffer also served as Business Development Manager at Wolters Kluwer Health. In this role, he helped to build an independent research group and life science consulting business. He was previously US Director of Sales and Marketing at Informa. Mr. Schaeffer received his Master in Business Administration from the Robert H. Smith School of Business and has a Bachelor of Arts in Sociology from the University of Maryland.
Adam Schaeffer, [email protected]
1.301.602.3297
Ms. Hoggatt covers the medical technology sector and some infectious disease and CNS indications. Ms. Hoggatt comes from Noble Financial where she was the Senior Medical Technology analyst. Prior to Noble, Ms. Hoggatt helped start the independent research firm, Variant Research with Dr. Weintraub and Dr. Henderson.
Before Variant she worked at Hibernia Southcoast Capital, where she was also a Medical Technology Analyst and a Vice President of Equity Research. Ms. Hoggatt began in the investment industry as an associate equity analyst at Morgan Keegan & Company covering medical devices and earned the title Associate Vice President of Equity Research. Her professional career has been focused on the healthcare sector and has included in-depth coverage of over thirty different companies in the Medical Technology and Medical Device industries, allowing her to share a wealth of knowledge and insight with our clients. Ms. Hoggatt received her Bachelors of Business Administration and Master of Accountancy from Millsaps College in Jackson, Mississippi.
Julie Schumacher Hoggatt, [email protected]
1.504.220.9366
http://www.inthought.com/mailto:[email protected]:[email protected]